Improving the conditions of animals not in good health which require medical treatment and thereby allowing the animals to return to their owners early is important for the animals and the owners as well as veterinarians and veterinary hospitals. Early recovery is desired particularly for animals hospitalized for medical treatment, such as a surgery. Favorable courses and stabilized pathological conditions, which accelerate the recovery of the hospitalized animals, are expected to contribute to the improvement of quality of life (QOL) of animals and owners and the reduction of burdens on veterinarians and veterinary hospitals.
Ghrelin is a hormone discovered in the stomach in 1999 and has an amino acid sequence consisting of 28 residues with a very rare chemical structure in which the amino acid at the 3rd position from the N terminus of the sequence is acylated with a fatty acid (Non Patent Literature 1 and Patent Literature 1). Ghrelin is an endogenous brain-gut hormone that acts on the growth hormone secretagogue-receptor 1a (GHS-R1a) (Non Patent Literature 2) and increases growth hormone (GH) secretion from the pituitary gland.
Ghrelin was first isolated from rats and purified as an endogenous GHS-R ligand for the GHS-R1a. Then, ghrelins having a similar primary structure were isolated from vertebrates other than rats, such as humans, mice, porcines, chickens, bovines, equines, ovines, canines, and felines, and amino acid sequences thereof are known (Patent Literature 1). Examples of ghrelins derived from animals are listed below.
Canine:(SEQ ID NO: 1)GSS (n-octanoyl) FLSPEHQKLQQRKESKKPPAKLQPR (SEQ ID NO: 2)GSS (n-octanoyl) FLSPEHQKLQRKESKKPPAKLQPR Feline:(SEQ ID NO: 3)GSS (n-octanoyl) FLSPEHQKVQRKESKKPPAKLQPR Rat:(SEQ ID NO: 4)GSS (n-octanoyl) FLSPEHQKAQQRKESKKPPAKLQPR (SEQ ID NO: 5)GSS (n-octanoyl) FLSPEHQKAQRKESKKPPAKLQPR Mouse:(SEQ ID NO: 6)GSS (n-octanoyl) FLSPEHQKAQQRKESKKPPAKLQPR Porcine:(SEQ ID NO: 7)GSS (n-octanoyl) FLSPEHQKVQQRKESKKPAAKLKPR Bovine:(SEQ ID NO: 8)GSS (n-octanoyl) FLSPEHQKLQRKEAKKPSGRLKPR Ovine:(SEQ ID NO: 9)GSS (n-octanoyl) FLSPEHQKLQRKEPKKPSGRLKPR Equine:(SEQ ID NO: 10)GSS (n-butanoyl) FLSPEHHKVQHRKESKKPPAKLKPR Chicken:(SEQ ID NO: 11)GSS (n-octanoyl) FLSPTYKNIQQQKGTRKPTAR (SEQ ID NO: 12)GSS (n-octanoyl) FLSPTYKNIQQQKDTRKPTAR (SEQ ID NO: 13)GSS (n-octanoyl) FLSPTYKNIQQQKDTRKPTARLH Human:(SEQ ID NO: 14)GSS (n-octanoyl) FLSPEHQRVQQRKESKKPPAKLQPR (SEQ ID NO: 15)GSS (n-octanoyl) FLSPEHQRVQ-RKESKKPPAKLQPR Monkey:(SEQ ID NO: 16)GSS (n-octanoyl) FLSPEHQRAQQRKESKKPPAKLQPR Dear:(SEQ ID NO: 17)GSS (n-octanoyl) FLSPEHQKLQ-RKEPKKPSGRLKPR (SEQ ID NO: 18)GSS (n-octanoyl) FLSPDHQKLQ-RKEPKKPSGRLKPR Goat:(SEQ ID NO: 19)GSS (n-octanoyl) FLSPEHQKLQ-RKEPKKPSGRLKPR Rabbit:(SEQ ID NO: 20)GSS (n-octanoyl) FLSPEHQKVQQRKESKKPAAKLKPR Wild turkey:(SEQ ID NO: 21)GSS (n-octanoyl) FLSPAYKNIQQQKDTRKPTARLHPR Goose:(SEQ ID NO: 22)GSS (n-octanoyl) FLSPEFKKIQQQNDPTKTTAKIHPR Japanese quail:(SEQ ID NO: 23)GSS (n-octanoyl) FLSPAYKNIQQQKNTRKPAARLHRR(Amino acid residues are expressed in the single letter code in the above list.)
The peptides listed above are peptides that have a specific structure in which a side chain hydroxyl group of the serine residue (S) at the 3rd position is acylated with a fatty acid, such as butanoic acid, octanoic acid, or decanoic acid. Other than ghrelin, no bioactive peptide having such a hydrophobic modification structure has been isolated from living organisms.
In addition to the peptide compounds listed above, examples of substances that act on the GHS-R1a include the GHRP-2, which is a peptide compound, and MK-0677, which is a low molecular weight compound (Non Patent Literature 4).
Recent studies have revealed that ghrelin increases appetite, that subcutaneous administration of ghrelin increases body weight and body fat (Non Patent Literatures 3 to 6), and that ghrelin has effects of improving cardiac function and the like (Non Patent Literatures 7 to 9). Furthermore, ghrelin has a GH secretagogue action and an appetite increasing action. Through the increased appetite, ghrelin is therefore expected to further effectively exhibit an action of burning fat and converting the fat into energy through a GH action and an effect of building muscle through an expressed anabolic action of GH (Non Patent Literature 9).
A more effective therapeutic agent for accelerating recovery is demanded to treat animals not in good health which require medical treatment, particularly to restore animals hospitalized for a surgery or the like early.